Early Prophylaxis Immunologic Challenge (EPIC) Study

Hemophilia A Clinical Trial

— EPIC  

Official title:

A Phase 3b Clinical Study to Assess Whether Regular Administration of ADVATE in the Absence of Immunological Danger Signals Reduces the Incidence Rate of Inhibitors in Previously Untreated Patients With Hemophilia A

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01376700
• Other study ID #: 061002
• Secondary ID: 2011-000410-18
• Status: Terminated
• Phase: Phase 3
• Start date: August 26, 2011
• Est. completion date: November 16, 2012

Study information

• Verified date: April 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to assess if a once-weekly prophylactic regimen of 25 IU/kg ADVATE started at or before 1 year of age and before the onset of a severe bleeding phenotype (ie, joint bleeding), together with the minimization of immunological danger signals, can reduce the incidence rate of inhibitor formation in PUPs with severe and moderately severe hemophilia A.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: November 16, 2012
• Est. primary completion date: November 16, 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 1 Year

Eligibility

Inclusion Criteria:

• Participants with severe and moderately severe hemophilia A (FVIII = 2%)

• Participants < 1 year of age

• Participants must have = 3 exposure days (EDs) to any FVIII concentrate or FVIII-containing product used for treatment of minor bleeds (bleeds requiring no more than 2 infusions per event), or for preventative or precautionary infusions following possible injury

• Participants with prior circumcision are allowed to enroll only if bleeding issues related to circumcision were the cause for the original diagnosis of hemophilia A and no more than 2 EDs of FVIII treatment were required

• Adequate venous access (without need for central venous access device (CVAD)-placement) as determined by the physician

• Written informed consent from legally authorized representative(s)

Exclusion Criteria:

• Life-threatening conditions (intracranial hemorrhage, severe trauma) or requirement for surgery at the time of enrollment

• Evidence of inhibitor = 0.6 Bethesda Unit (BU) in Nijmegen-modified Bethesda Assay at study start (samples may be retested using lupus-insensitive inhibitor tests to reduce the number of false positive inhibitor test results)

• Inherited or acquired hemostatic defect other than hemophilia A

• Any clinically significant, chronic disease other than hemophilia A

• Known hypersensitivity to ADVATE or any of its constituents

• Any planned elective surgery that cannot be postponed until after the first 20 EDs

• Participation in the Hemophilia Inhibitor Previously Untreated Patient Study

• Application of red blood cell, platelet, or leukocyte concentrates, or plasma

• Administration of any medication affecting coagulation or platelet function

• Systemic administration of any immunomodulatory drug (eg, chemotherapy, intravenous glucocorticoids)

• Participation in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or during the course of this study

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Biological:
• Recombinant antihemophilic factor, plasma/albumin-free method (rAHF-PFM)
Intravenous infusion at a dose of 25 ± 5 IU/kg once per week. After 20 exposure days, the weekly infusions should be continued for as long as possible following the early prophylaxis period. If required by the clinical situation, dosing may be increased to twice weekly or even three times weekly after 20 exposure days, while keeping the low dose.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Baxalta now part of Shire	Baxter Innovations GmbH

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Canada,  Czechia,  Germany,  Lithuania,  Netherlands,  Poland,  Russian Federation,  Serbia,  Spain, 

References & Publications (1)

Auerswald G, Kurnik K, Aledort LM, Chehadeh H, Loew-Baselli A, Steinitz K, Reininger AJ; EPIC clinical study group. The EPIC study: a lesson to learn. Haemophilia. 2015 Sep;21(5):622-8. doi: 10.1111/hae.12666. Epub 2015 Apr 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Severe and Moderately Severe Hemophilia A (FVIII = 2%) With Factor VIII (FVIII) Inhibitor Formation Within the First 50 Exposure Days to ADVATE	Inhibitor testing will be performed in the central laboratory and a non-zero result must be confirmed in the central laboratory as soon as possible, preferably 1 week after inhibitor testing. Confirmed FVIII inhibitor is defined as any FVIII inhibitor assay result equal or greater than 0.6 Bethesda Units (BU)/mL confirmed by the central laboratory on 2 consecutive samples, i.e. at least 2 positive inhibitor results (including the first positive inhibitor test, in accordance with the study protocol) assessed as either: - i. High FVIII inhibitor titer (> 5 BU/mL) or - ii. Low FVIII inhibitor titer (=0.6 - =5.0 BU/mL).	50 exposure days to ADVATE
Secondary	Number of Participants With Severe Hemophilia A (FVIII = 1%) With Factor VIII (FVIII) Inhibitor Formation Within the First 50 Exposure Days to ADVATE	Inhibitor testing will be performed in the central laboratory and a non-zero result must be confirmed in the central laboratory as soon as possible, preferably 1 week after inhibitor testing. Confirmed FVIII inhibitor is defined as any FVIII inhibitor assay result equal or greater than 0.6 Bethesda Units (BU)/mL confirmed by the central laboratory on 2 consecutive samples, i.e. at least 2 positive inhibitor results (including the first positive inhibitor test, in accordance with the study protocol) assessed as either: - i. High FVIII inhibitor titer (> 5 BU/mL) or - ii. Low FVIII inhibitor titer (=0.6 - =5.0 BU/mL).	50 exposure days to ADVATE
Secondary	Number of Exposure Days of Treatment With Advate Prior to First Positive Factor VIII (FVIII) Confirmed Inhibitor Assessment	Confirmed inhibitor is defined as any FVIII inhibitor assay result equal or greater than 0.6 BU/mL confirmed by the central laboratory on 2 consecutive samples, i.e. at least 2 positive inhibitor results (including the first positive inhibitor test, in accordance with the study protocol) assessed as either: - i. High FVIII inhibitor titer (> 5 BU/mL) or - ii. Low FVIII inhibitor titer (=0.6 - =5.0 BU/mL).	50 exposure days to ADVATE
Secondary	Number of Participants With Low-titer, High-titer, Transient, and All Factor VIII (FVIII) Inhibitors	- High FVIII inhibitor titer (> 5 Bethesda Unit (BU)/mL) - Low FVIII inhibitor titer (=0.6 - =5.0 BU/mL)	50 exposure days to ADVATE
Secondary	Number, Type, and Severity of All Bleeds Experienced When Different Prophylactic Dosing Frequencies Are Used (Once or Twice Per Week and Unknown Frequency)	Nominal Dosing Frequency: - 1 time per week - 2 times per week - Unknown dosing frequency (UK) Bleeding Type (BT): - Skin - Muscle and Soft Tissue - Mucosal - Joint - Other - Multiple - Total Bleeding severity: - Minor - Moderate - Severe - Total	50 exposure days to ADVATE
Secondary	Number and Type of Surgeries	- Elective surgery is not allowed during period of first 20 exposure days (EDs) - Peripherally inserted central catheter (PICC)	50 exposure days to ADVATE
Secondary	Correlation of Known Risk Factors to Factor VIII (FVIII) Inhibitor Formation		50 exposure days to ADVATE
Secondary	Total Factor VIII (FVIII) Consumption by Participant		50 exposure days to ADVATE
Secondary	FVIII-Specific Antibody Isotype for All Participants at Study Entry and Every 10 Exposure Days (EDs)		50 exposure days to ADVATE
Secondary	Number of Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs) at Least Possibly Related to ADVATE	Possibly or probably related adverse events	50 exposure days to ADVATE